Cytotoxic activity of ethanolic extracts of Lippia graveolens HBK leaves and stem against lung cancer cell line SK-LU-1 / Actividad citotóxica de extractos etanólicos de hoja y tallos de Lippia graveolens HBK contra la línea celular de cáncer de pulmón SK-LU-1

Lippia graveolens HBK (Verbenaceae) is an aromatic herb of economic importance in Mexico, known as oregano. The leaves are used as condiments, and people use this species for respiratory and digestive disorders. The aim of this work was to evaluate the cytotoxic effect of ethanolic extracts obtained from free-oil leaves (L9) and stem (S15), against lung cancer cell line SK-LU-1, through tetrazolium salt (MTT) assay. Extracts concentrations of 0.3 to 300 µg/mL were used and HFF-1 as normal control cells. Both L9 and S15 extracts, showed cytotoxic effect, although stem was stronger than leaves and without damage to normal cell control. The phenolic compounds caffeic acid and acacetin werein higher concentration in L9, whereas naringenin, taxifolin, eriodictyol, luteolin, and apigenin had higher concentrations in S15. The ethanolic extracts of L. graveolens have excellent cytotoxic activity, and have a wide possibility of use in lung cancer treatment.

Lippia graveolens HBK. (Verbenaceae) es una hierba aromática de importancia económica en México, conocida como orégano. Las hojas se usan como condimento y en medicina tradicional se utiliza para aliviar malestares respiratorios y digestivos. El objetivo de este trabajo fue evaluar el efecto citotóxico de extractos etanólicos obtenidos de hojas sin aceite (L9) y tallo (S15), sobre la línea celular de cáncer de pulmón SK-LU-1, mediante el ensayo de la sal de tetrazolium (MTT). Los extractos se aplicaron a concentraciones de 0,3 a 300 µg/mL y se utilizaron células HFF-1 como control normal. Tanto los extractos L9 como S15 mostraron efecto citotóxico, aunque el efecto del tallo fue mayor al de las hojas y sin daño al control celular normal. Los compuestos fenólicos ácido cafeico y acacetina se encontraron en mayor concentración en L9, mientras que naringenina, taxifolina, eriodictyol, luteolina y apigenina tuvieron mayor concentración en S15. Los extractos etanólicos de L. graveolens tienen una excelente actividad citotóxica, con amplia posibilidad de utilizar en el tratamiento de cáncer de pulmón.

Synthesis of new derivatives of 21-imidazolyl-16-dehydropregnenolone as inhibitors of 5α-reductase 2 and with cytotoxic activity in cancer cells.

The aim of this study was to synthesize several 16-dehydropregnenolone derivatives containing an imidazole ring at C-21 and a different ester moiety at C-3 as inhibitors of 5α-reductase 1 and 2 isoenzymes. Their binding capacity to the androgen receptor (AR) was also studied. Additionally, we evaluated their pharmacological effect in a castrated hamster model and their cytotoxic activity on a panel of cancer cells (PC-3, MCF7, SK-LU-1). The results showed that only the derivatives with an alicyclic ester at C-3 showed 5α-R2 enzyme inhibition activity, the most potent of them being 21-(1H-imidazol-1-yl)-20-oxopregna-5,16-dien-3ß-yl-cyclohexanecarboxylate with an IC50 of 29nM. This is important because prostatic benign hyperplasia is directly associated with the presence of 5α-R2. However, all the derivatives failed to inhibit 5α-R1 or bind to the AR. These alicyclic ester derivatives decreased the weight and size of androgen-dependent glands in the hamster, indicating they are very active in vivo and are not toxic. In addition, the 21-(1H-imidazol-1-yl)-20-oxopregna-5,16-dien-3ß-yl-acetate derivative showed the highest cytotoxic activity on the three cancer cell lines studied. It is therefore important in the synthesis of steroidal compounds to consider the size of the ester moiety at C-3 of the steroid skeleton, which is key in obtaining biological activity, as observed in this experiment.